Bioreactor operation

Batch mixed reactor There are three principal modes of bioreactor operation (a) batch (b) fed batch (c) continuous. 

Glasgow LA, Jones GT, Erickson LE (1989) Hydrodynamic characterization of airlift bioreactor operation. In Two-Phase Flows, Tapie, Tawan... 

Figure 12.6 Fed-batch Bioreactor Operability Region [reprinted from the Canadian Journal of Chemical Engineering with permission]...

Fluidization Regime. As for traditional fluidization applications, the fluidization regime—dispersed bubble, coalesced bubble, or slugging—in which a three-phase fluidized bioreactor operates depends strongly on the system parameters and operating conditions. Generally, desirable fluidization is considered to be characterized by stable operation with uniform phase holdups, typical of the dispersed bubble regime. It would be useful to be able to predict what conditions will produce such behavior. 

Effluent is drawn off from a side port. Under conditions in which a conventional three-phase fluidized bed bioreactor operated in an unstable manner because of gas logging, the new bioreactor converted glucose to ethanol at a 27% higher rate. Saccharomyces cerevisiae was grown in alginate beads for this reaction. 

The development of novel bioreactors and bioreactor operating strategies has the potential to improve the performance of cell culture systems. Some progress has been made in this area to enhance foreign protein production in plant tissue culture. 

The above generalised forms of equations can be simplified to fit particular cases of bioreactor operation. 

In this paper the fundamental aspects of process development for the production of core and virus-like particles with baculovirus infected insect cells are reviewed. The issues addressed include particle formation and monomer composition, chemical and physical conditions for optimal cell growth, baculovirus replication and product expression, multiplicity of infection strategy, and scale-up of the process. Study of the differences in the metabolic requirements of infected and non-infected cells is necessary for high cell density processes. In the bioreactor, the specific oxygen uptake rate (OURsp) plays a central role in process scale-up, leading to the specification of the bioreactor operational parameters. Shear stress can also be an important variable for bioreactor operation due to its influence on cell growth and product expression. 

In this part the determination of critical variables for bioreactor operation and scale-up are reviewed. Special focus is put on the specific oxygen uptake rate (OURsp) and its influence upon the specification of bioreactor operational parameters. Shear stress can also be an important variable for process design and its importance in cell growth and product expression is discussed. 

Volumetric productivity is a good performance index in what concerns the optimization of bioreactor operation. It can be used in process improvement at a defined scale and also for process scale-up, since it is a dimensionless variable. Therefore bioreactor operation and scale-up for CLP and VLP production will be addressed as the identification of the operational conditions that result in the best volumetric productivity. 

Bioreactor operation and scale-up are not completely independent processes and should be assessed as different aspects of the same problem. Bioreactor operation must then consider process scale-up not only as the next step but also, as in the classic scale-down method, as a starting point. This means that bioreaction design should be done in scalable systems. A scalable system has to be inherently simple and reliable in operation and control, for easy validation and control in a production facility [56]. 

The bioreactor operation mode is normally defined at the outset of process configuration. Insect cells have been cultured in almost all known cultivation modes batch [10], repeated-batch [70], perfusion [71-74], fed-batch [75, 76], semi-continuous [77,78] and continuous [79]. In spite of this multitude of different strategies, the batch or, eventually, fed-batch mode is normally preferred due to the lytic infection cycle of the baculovirus. 

Cruz et al. [69] have optimised bioreactor operational conditions for HIV-VLPs production using the concept of minimising local shear stress, i.e., they assumed that all the energy liberated by the stirring turbine was dissipated... 

As with refining and petrochemical processes, bioprocesses must be operated automatically so as to achieve a consistent production of various bioproducts in a cost-effective way. In particular, there is a strong demand to optimize bioprocesses by controlling them automatically to promote labor-saving operations. To achieve this, it is necessary to understand what is happening in a bioreactor (instrumentation) and to properly manipulate the control variables that affect the performance of a bioreactor operation (control). 

Oxidation-Reduction Potential Oxidation-reduction potential (ORP) is measured by an ORP probe, which is effective to monitor the redox potential of a bioreactor operated under microaerobic conditions that cannot be successfully measured by a DO probe. The measurements of redox are sometimes influenced by changes in the pH and mineral concentrations of a culture broth. 

Some technical limitations to solid-phase PAH bioremediation exist. As compared with bioreactor operations, extended periods of treatment time will predictably be required with solid-phase PAH bioremediation operations. In many cases this is quite acceptable, especially when solid-phase systems are designed to... 

In this operation mode, it is possible to mitigate the major limitation of continuous cultures, that is, the low productivity due to the loss of cells in the bioreactor outlet. In perfusion, this issue is overcome by using a cell retention device to maintain cells inside the bioreactor. Figure 9.17 shows a scheme of a stirred-tank bioreactor operating in perfusion mode, as well as the kinetic behavior of a perfusion run. 

Parameter Stirred-tank bioreactors operated in batch and fed-batch mode Stirred-tank bioreactors operated in perfusion mode Heterogeneous bioreactors (packed-bed or hollow-fiber) operated in perfusion mode... 

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